A Novel Insight into the Cardiotoxicity of Antineoplastic Drug Doxorubicin

Doxorubicin is a commonly used antineoplastic agent in the treatment of many types of cancer. Little is known about the interactions of doxorubicin with cardiac biomolecules. Serious cardiotoxicity including dilated cardiomyopathy often resulting in a fatal congestive heart failure may occur as a consequence of chemotherapy with doxorubicin. The purpose of this study was to determine the effect of exposure to doxorubicin on the changes in major amino acids in tissue of cardiac muscle (proline, taurine, glutamic acid, arginine, aspartic acid, leucine, glycine, valine, alanine, isoleucine, threonine, lysine and serine). An in vitro interaction study was performed as a comparison of amino acid profiles in heart tissue before and after application of doxorubicin. We found that doxorubicin directly influences myocardial amino acid representation even at low concentrations. In addition, we performed an interaction study that resulted in the determination of breaking points for each of analyzed amino acids. Lysine, arginine, β-alanine, valine and serine were determined as the most sensitive amino acids. Additionally we compared amino acid profiles of myocardium before and after exposure to doxorubicin. The amount of amino acids after interaction with doxorubicin was significantly reduced (p = 0.05). This fact points at an ability of doxorubicin to induce changes in quantitative composition of amino acids in myocardium. Moreover, this confirms that the interactions between doxorubicin and amino acids may act as another factor most likely responsible for adverse effects of doxorubicin on myocardium.     

Apoferritin Modified Magnetic Particles as Doxorubicin Carriers for Anticancer Drug Delivery

Magnetic particle mediated transport in combination with nanomaterial based drug carrier has a great potential for targeted cancer therapy. In this study, doxorubicin encapsulation into the apoferritin and its conjugation with magnetic particles was investigated by capillary electrophoresis with laser-induced fluorescence detection (CE-LIF). The quantification of encapsulated doxorubicin was performed by fluorescence spectroscopy and compared to CE-LIF. Moreover, the significant enhancement of the doxorubicin signal was observed by addition of methanol into the sample solution.     

Lead Free Ammunition without Toxic Propellant Gases

Environmental and health considerations have encouraged the development of ammunition with substitutes for lead and other heavy metals. In general, the emission products from munitions containing nitro‐based propellants are highly complex mixtures of gases, vapors, and solid particles. The major combustion products are H₂O, CO, CO₂, H₂, and N₂. In addition, compounds including hydrogen cyanide (HCN), ammonia (NH₃), methane (CH₄), nitrogen oxides, benzene, acrylonitrile, toluene, furan, aromatic amines, benzopyrene, and various polycyclic aromatic hydrocarbons are detected in minor concentrations. Many of the identified chemical species have severe toxicological properties, and some of the compounds do even have mutagenic effects. Gun smoke emission is a concern because its exposure to humans may be substantial during military and civilian police training, as respiratory protection equipment is not routinely worn. In this work we study the compositions of some of the main decomposition products, experimentally as well as theoretically. The concept of frozen equilibrium at around 1500–2000 K appears to apply for CO, CO₂, and H₂. However, the trace species in the combustion mixtures appear theoretically to be present in negligible concentrations. Our measured results are many orders of magnitude higher than theoretical results in open space. We forecast that future development of gun powder will focus on reducing the amount of toxic trace species.     

Isocyanate‐Free and Dual Curing of Smokeless Composite Rocket Propellants

Traditional composite rocket propellants are cured by treatment of hydroxyl‐terminated prepolymers with polyfunctional aliphatic isocyanates. For development of smokeless composite propellants containing nitramines and/or ammonium dinitramide (ADN), energetic binder systems using glycidyl azide polymer (GAP) are of particular interest. Polyfunctional alkynes are potential isocyanate‐free curing agents for GAP through thermal azide‐alkyne cycloaddition and subsequent formation of triazole crosslinkages. Propargyl succinate or closely related aliphatic derivatives have previously been reported for such isocyanate‐free curing of GAP. Herein, we present the synthesis and use of a new aromatic alkyne curing agent, the crystalline solid bisphenol A bis(propargyl ether) (BABE), as isocyanate‐free curing agent in smokeless propellants based on GAP, using either octogen (HMX) and/or prilled ADN as energetic filler materials. Thermal and mechanical properties, impact and friction sensitivity and ballistic characteristics were evaluated for these alkyne cured propellants. Improved mechanical properties could be obtained by combining isocyanate and alkyne curing agents (dual curing), a combination that imparted better mechanical properties in the cured propellants than either curing system did individually. The addition of a neutral polymeric bonding agent (NPBA) for improvement of binder‐filler interactions was also investigated using tensile testing and dynamic mechanical analysis (DMA). It was verified that the presence of isocyanates is essential for the NPBA to improve the mechanical properties of the propellants, further strengthening the attractiveness of dual cure systems.     

Breakage behaviour of spherical granulates by compression

This paper describes the deformation and breakage behaviour of granulates in single particle compression test. Three industrial spherical granulates—γ-Al₂O₃, the synthetic zeolite Köstrolith^® and sodium benzoate (C₆H₅COONa) were used as model materials to study the mechanical behaviour from elastic to plastic range. The elastic compression behaviour of granulates is described by means of force-displacement curves, by application of Hertz-Huber contact theory and continuum mechanics. An elastic-plastic contact model was proposed to describe the deformation behaviour of elastic-plastic granules. The effects of granulate size and stressing velocity on the breakage force and contact stiffness during elastic and elastic-plastic displacement are examined. It is shown that the zeolite granulates with elastic-plastic behaviour have viscous properties as well. Breakage mechanisms of granulates during elastic, elastic-plastic and plastic deformation are also explained. The breakage probability is approximated by Weibull distribution function. The behaviour of the granulate during compression under the repeated loading-unloading conditions was investigated.     

The Role of Exosomes in Cancer Progression

Early detection, characterization and monitoring of cancer are possible by using extracellular vesicles (EVs) isolated from non-invasively obtained liquid biopsy samples. They play a role in intercellular communication contributing to cell growth, differentiation and survival, thereby affecting the formation of tumor microenvironments and causing metastases. EVs were discovered more than seventy years ago. They have been tested recently as tools of drug delivery to treat cancer. Here we give a brief review on extracellular vesicles, exosomes, microvesicles and apoptotic bodies. Exosomes play an important role by carrying extracellular nucleic acids (DNA, RNA) in cell-to-cell communication causing tumor and metastasis development. We discuss the role of extracellular vesicles in the pathogenesis of cancer and their practical application in the early diagnosis, follow up, and next-generation treatment of cancer patients.     

NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases

Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia—a locus for craniofacial sensory nerves—were used to examine how NGF affects the Ca²⁺-dependent release of a pain mediator, calcitonin gene-related peptide (CGRP), that is triggered by activating a key signal transducer, transient receptor potential vanilloid 1 (TRPV1) with capsaicin (CAP). Measurements utilised neurons fed with or deprived of NGF for 2 days. Acute re-introduction of NGF induced Ca²⁺-dependent CGRP exocytosis that was inhibited by botulinum neurotoxin type A (BoNT/A) or a chimera of/E and/A (/EA), which truncated SNAP-25 (synaptosomal-associated protein with Mr = 25 k) at distinct sites. NGF additionally caused a Ca²⁺-independent enhancement of the neuropeptide release evoked by low concentrations (<100 nM) of CAP, but only marginally increased the peak response to ≥100 nM. Notably, BoNT/A inhibited CGRP exocytosis evoked by low but not high CAP concentrations, whereas/EA effectively reduced responses up to 1 µM CAP and inhibited to a greater extent its enhancement by NGF. In addition to establishing that sensitisation of sensory neurons to CAP by NGF is dependent on SNARE-mediated membrane fusion, insights were gleaned into the differential ability of two regions in the C-terminus of SNAP-25 (181–197 and 198–206) to support CAP-evoked Ca²⁺-dependent exocytosis at different intensities of stimulation.     

Strength distribution of particles under compression

From time immemorial people dealt with size reduction processes (mill, mineral liberation, etc.). As time has passed industrial units for comminution processes have become larger and more sophisticated, but still they perform with low efficiencies [1], [2] and [3]. The strength of a particle is one of its most crucial characteristics due to the mechanical stresses experienced by each particle within an industrial unit. This is because the final size of particles is mostly dependant on the strength distribution of the raw material [4]. In this present study, the ability of a number of statistical formulations to accurately describe the strength distribution of particles was examined. Additionally, selected equations were analyzed and a general expression including the effect of the material and particle size was developed. A number of approaches to define particle strength were considered, and strength in terms of crushing force was chosen. Particle strength in terms of force and in terms of energy was also compared and found to be size independent. Finally, particle strength in terms of stress was examined and compared to the particle strength in terms of force.The ability to describe the compression strength distribution will significantly improve the accuracy of the comminution processes simulation, design and optimization.     

Einfluss der Feuchtebeladung bei der Druckbeanspruchung von Granulaten

The material behavior of γ‐Al₂O₃‐, zeolite 4A‐ und sodium benzoate granules at compression has been experimentally studied. The material behavior has been found to be dominant elastic, elastic‐plastic and dominant plastic. Additionally, the influence of moisture content on the material behavior has been investigated. The force‐displacement curves have been approximated using suitable mechanical models.     

Optimization of a Continuous Precipitation Process to Produce Nanoscale BaSO4

The effect of supersaturation, reaction temperature, and mixing intensity on particle size was investigated. Sterical stabilization of barium sulfate suspensions was applied to prevent formation of agglomerates. This allowed a reactant ratio of 1:1, thus maximizing product yield. The local supersaturation is strongly affected by the mixing intensity that can be characterized by Reynolds numbers. The significant decrease in particle size was observed by increasing the Reynolds number from 600 to 8000. A higher reactant concentration leads to a higher degree of supersaturation, and finer particles are precipitated. The particle size can be reduced with increasing reactant concentration. The degree of supersaturation increases with temperature reduction, i.e., the particle size will be reduced at low temperature. In addition, nucleation and growth kinetics are changed in a way that reduces the particle size. The optimized lab‐scale process is capable of producing over 1 kg h^–1 of nanoscaled BaSO₄ with a median diameter of 75 nm.